Saucier D M, Kavaliers M
Department of Psychology, University of Western Ontario, London, Canada.
Brain Res. 1994 Feb 21;637(1-2):292-6. doi: 10.1016/0006-8993(94)91247-5.
The present study examined the effects of the competitive NMDA antagonist, NPC 12626, on the analgesic effects of the specific kappa opiate receptor agonist, U69,593, in male deer mice. Intraperitoneal (i.p.) administration of NPC 12626 had no effect on the basal nociceptive sensitivity of reproductive male deer mice, as measured by latency of response to a thermal (50 degrees C) surface. NPC 12626 dose-dependently (0.05-1.0 mg/kg) reduced U69,593-induced analgesia. NPC 12626 at 1.0 mg/kg attenuated U69,593-induced analgesia in a manner comparable to that produced by the specific kappa opiate antagonist, nor-binaltorphimine. In contrast, this dose of NPC 12626 potentiated the analgesia produced by the predominantly mu agonist morphine (1.0 mg/kg). The non-competitive NMDA antagonist, MK-801, which has been previously indicated to affect kappa opiate analgesia, significantly reduced at 1.0 mg/kg, but did not block, the analgesia produced by U69,593 and in contrast to NPC 12626, slightly reduced morphine-induced analgesia. These findings suggest that the NMDA antagonist, NPC 12626, may, either directly or indirectly, have effects on kappa opiate receptor mediated mechanisms.
本研究检测了竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂NPC 12626对雄性鹿鼠体内特异性κ阿片受体激动剂U69,593镇痛作用的影响。腹腔注射NPC 12626对成年雄性鹿鼠的基础伤害性感受敏感性没有影响，这一敏感性通过对热（50摄氏度）表面的反应潜伏期来衡量。NPC 12626呈剂量依赖性（0.05 - 1.0毫克/千克）地降低了U69,593诱导的镇痛作用。1.0毫克/千克的NPC 12626减弱U69,593诱导的镇痛作用的方式，与特异性κ阿片拮抗剂去甲二氢吗啡酮产生的作用方式相当。相比之下，该剂量的NPC 12626增强了主要为μ激动剂的吗啡（1.0毫克/千克）产生的镇痛作用。非竞争性NMDA拮抗剂MK-801，先前已表明其会影响κ阿片镇痛作用，在剂量为1.0毫克/千克时可显著降低但不阻断U69,593产生的镇痛作用，并且与NPC 12626相反，会轻微降低吗啡诱导的镇痛作用。这些发现表明，NMDA拮抗剂NPC 12626可能直接或间接对κ阿片受体介导的机制产生影响。
